2-deoxy-2,2-disubstituted-ribono-1,4-lactone and derivatives thereof are important intermediates of a variety of anti-viral and anti-tumor active ingredients. For example, these compounds were used as raw materials in the development of anti-hepatitis C drugs PSI-7977 and R7128 with the following structures by Pharmasset Company. The two anti-hepatitis C drugs are currently undergoing clinical experiments.

The routes for preparing the 2-deoxy-2,2-disubstituted-ribono-1,4 -lactone and derivatives thereof have been reported. For example, a preparation method as shown in Scheme 1 was reported in WO2008045419 and J. Org. Chem, 2009, 74, 6819-6824, in which the asymmetric synthesis method is applied to control the chirality of C-2 position, however the disadvantages thereof is longer route, relatively complicated operation and low yield. Further, in the preparation method as shown in Scheme 1, it is not easy to control the quality of the intermediates resulting in the unstable quality of the final product, because some of the intermediates are unstable.

A preparation method as shown in Scheme 2 was reported in US20080145901 and Tetrahedron: Asymmetry, 2009, 20, 305-312.

In the chemical reaction according to the above method, the two steps of selective enzymatic hydrolysis and crystallization are carried out without controlling the chirality of C-2 position, so as to achieve the purpose of resolution. However, this approach requires a large amount of buffer or the like, has relatively low preparation efficiency, and is not suitable for large-scale application. in addition, since the first step of reaction requires low temperature reaction condition, in which strong base such as lithium diisopropylamide (LDA) and so on has to be used and the harsh reaction conditions are required, it has relatively high demand on the equipment.
A preparation method as shown in Scheme 3 was reported in WO2008090046, in which the title compound was synthesized by replacing ethoxy in US20080145901 with non-chiral auxiliary group having a large steric hindrance (for example, pyrrole, thiophenol, or benzoxazolone) to form large sterically hindered amide or thiophenol ester. However, in this method, the chiral selectivity is not high, and the maximal the de value of the obtained product is only 56%.

Therefore, it is still need to find out a method for preparing the (2R)-2-deoxy-2,2-disubstituted-ribono-1,4-lactone with high steric selectivity, high yield and low cost, and suitable for industrial application.